JP5107730B2 - Ceramide dispersant and ceramide composition - Google Patents

Description

  The present invention relates to a cosmetic, quasi-drug, skin external preparation or hair preparation in the pharmaceutical field, a dispersant that can be uniformly dispersed in an aqueous medium by adding a cellooligosaccharide to a sparingly soluble / hardly dispersible ceramide, and The present invention relates to a ceramide composition that is uniformly dispersed and can be stably stored.

Ceramide is a component of stratum corneum intercellular lipids, contributes to the barrier function of the skin, is said to protect the skin from external enemies such as dryness and dust, and maintain the health of the epidermis.
Insufficient ceramide has an adverse effect on skin health. Therefore, cosmetics, quasi-drugs, and pharmaceuticals have been formulated and replenished as a skin external preparation or hair preparation.
Ceramide has a problem that it has a poor affinity for both aqueous and oil-based media, is difficult to uniformly disperse, and is difficult to prepare as a preparation. In addition, once dispersed, problems such as precipitation during storage and water separation may occur.

  Conventionally, attempts have been made to blend organic solvents such as alcohols and surfactants for uniform dispersion or storage stability of ceramide. Non-Patent Document 1 discloses the preparation of an emulsion in which intercellular lipid components extracted with acetone and ether are repeatedly heated and cooled together with water.

According to these methods, ceramide is certainly dispersed uniformly. However, organic solvents and / or surfactants used for extraction or dispersion have a concern of causing irritation when applied to sensitive skin or the like, and the amount used is also limited. Further, in order to obtain a safe preparation, it is necessary to remove the organic solvent and the like, which causes a problem that the process becomes complicated and the cost is increased.
Therefore, when ceramide is used as an external preparation, uniform dispersion using a substance that is not irritating, safe and excellent in stability has been desired.

  Patent Document 1 describes a lamellar structure regenerating agent in skin horny layer cells containing glucose and / or raffinose, and a lamellar structure regenerating agent in skin horny layer cells characterized by containing glucose and oligosaccharides. Has been. In this document, as a lamellar structure regenerating agent, an external preparation containing glucose as an essential component, and containing at least one selected from raffinose, melibiose, trehalose, sucrose, maltose, cellobiose, gentianose, stachyose, and cyclodextrin as oligosaccharides There is a description.

  In addition, Patent Document 1 (Examples) discloses that as a part of a method for verifying barrier properties on the skin, a lamella is mixed in a stratum corneum intercellular lipid model containing ceramide, thereby lamellar in an aqueous medium. An example is shown that facilitates the formation of a structure.

  However, Patent Document 1 discloses that the use of a composition in which saccharides are added to ceramide as an external preparation for skin, the incorporation of saccharides into ceramide allows easy uniform dispersion and further enhances storage stability. unknown. In addition, there is no description or suggestion about features, uses, and examples related to cellooligosaccharides including cellobiose. Therefore, the preparation of the external preparation of the present invention is essentially different from the ceramide dispersant on the preparation. Therefore, as in the present invention, a ceramide dispersant having a cellooligosaccharide having a cellobiose content in a specific range as an active ingredient, non-irritating, safe and excellent in stability has not been known.

Functional cosmetics IV, CMC Publishing, 2006, p. 39-47 JP 2006-45186 A

  The present invention relates to a cosmetic, quasi-drug, skin external preparation or hair preparation in the pharmaceutical field, a dispersant that can be uniformly dispersed in an aqueous medium by adding a cellooligosaccharide to a sparingly soluble / hardly dispersible ceramide, and It is an object of the present invention to provide a ceramide composition in which ceramide is uniformly dispersed in an aqueous medium and can be stably stored.

The present inventors have found that a cellooligosaccharide having a specific sugar composition uniformly disperses ceramide and enhances storage stability, and has made the present invention.
That is, the present invention is as follows.
(1) A ceramide composition containing ceramide dispersed in an aqueous medium using a ceramide dispersant containing cellooligosaccharide, comprising 0.005% by mass or more of cellooligosaccharide relative to ceramide, and further containing 0 A ceramide composition comprising 5 to 50% by mass of a fatty acid and 0.5 to 90% by mass of sterol and / or a sterol derivative with respect to ceramide.
(2) The cellobiose content in the cellooligosaccharide is 70% by mass or more, and the content of one or more sugars selected from cellotriose, cellotetraose, cellopentaose and cellohexaose is 30% by mass or less (1 The ceramide composition as described in 1.).
(3) The ceramide composition according to (1) or (2), which is used as a skin barrier function improving agent.

  By adding the ceramide dispersant containing the cellooligosaccharide of the present invention to the hardly soluble / hardly dispersible ceramide, a ceramide composition in which the ceramide is uniformly dispersed in the aqueous medium and can be stably stored is obtained.

The present invention will be specifically described below, particularly focusing on preferred embodiments thereof.
The ceramide dispersant of the present invention needs to contain a cellooligosaccharide.
Cellooligosaccharide is a general term for sugars in which two or more molecules of glucose such as cellobiose, cellotriose, cellotetraose, cellopentaose, cellohexaose and the like are β-1,4-linked. Is included.

  In the cellooligosaccharide of the present invention, the cellobiose content is 70% by mass or more, and the content of one or more sugars selected from cellotriose, cellotetraose, cellopentaose and cellohexaose is 30% by mass or less. preferable. In the cellooligosaccharide of the present invention, the glucose content is preferably 5.0% by mass or less.

  The cellobiose content in the cellooligosaccharide of the present invention is preferably 70% by mass or more. Cellobiose has the action of uniformly dispersing ceramide, and the higher the content, the better the effect of the present invention. Therefore, the cellobiose content is preferably 80% by mass or more, and more preferably 90% by mass or more.

  The cellooligosaccharide of the present invention preferably has a content of one or more sugars selected from cellotriose, cellotetraose, cellopentaose and cellohexaose of 30% by mass or less. Cellooligosaccharides have lower water solubility as the molecular weight increases. Therefore, when used in an aqueous medium, the amount added is limited, so the smaller the better. The content is preferably 10% by mass or less, more preferably 5% by mass or less, and particularly preferably 3% by mass or less.

  In the cellooligosaccharide of the present invention, the glucose content is preferably 5.0% by mass or less. Glucose content has no effect on ceramide liquid crystal formation and storage stability, but glucose reacts with amino acids and components that shake the amino group of protein sugar, causing browning of the formulation and deactivation of active ingredients It becomes. Therefore, the lower the glucose content is, the more preferable it is because the browning and the deactivation of the active ingredient can be suppressed. The glucose content is preferably 3.8% by mass or less, and more preferably 2% by mass or less.

Below, the analysis method of the cellooligosaccharide and glucose content in the ceramide dispersing agent of this invention is described. The cellooligosaccharide of the present invention is dissolved in pure water at a concentration of 1% by mass and then subjected to high performance liquid chromatography (chromatography system: manufactured by Shimadzu Corporation, trade name: SCL-10A, column: manufactured by Shimadzu Corporation, trade name: Asahipak NH ₂ P-50, mobile phase: acetonitrile / water = 75/25 (volume ratio)). The sugar composition of cellooligosaccharides is the mass percentage of the cell biose, cellotriose, cellotetraose, cellopentaose, cellohexaose peak area in the chromatogram obtained by the above method, and occupies the total mass. expressed. The content rate of glucose is also obtained by the same method, and is expressed as a percentage of the mass of glucose with respect to the total mass calculated from the peak areas of cellobiose and glucose.

Next, the manufacturing method of the cellooligosaccharide of this invention is demonstrated.
The origin of the cellooligosaccharide of the present invention is not particularly limited, and may be one produced by hydrolysis of a cellulosic substance, one produced by condensation or sugar transfer of a monosaccharide such as glucose or a derivative thereof, What was obtained by the decomposition method is preferable in terms of safety.

  Cellulosic substances used for enzymatic degradation may be plant or animal, and may be derived from natural products such as wood, bamboo, cotton, ramie, squirts, bagasse, kenaf, wheat, rice, and bacterial cellulose. Fibrous materials, or regenerated cellulose obtained by dissolving them in a solvent once, or those obtained by subjecting them to chemical treatment to form cellulose derivatives may be used, and one or more of the above may be used in combination. Among these, natural cellulosic substances that do not undergo dissolution or chemical treatment are preferable because the obtained cellooligosaccharides do not contain solvents or chemical substances harmful to the human body. Moreover, it is preferable to use a cellulosic substance in the state of a refined pulp, and there is no restriction | limiting in particular in the refinement | purification method of a pulp, You may use any pulp, such as a sulfite pulp, a kraft pulp, and NBKP pulp.

  In the case of enzymatically decomposing a cellulosic material, the cellulosic material used is a cellulosic material that has been hydrolyzed once and partially hydrolyzed to an average polymerization degree of 700 or less. It is preferable in terms of improvement. Furthermore, it is possible to use a cellulosic material having a specific degree of polymerization with an average particle size of 100 μm or less and a colloidal cellulose component content of 10% by mass or more to improve the enzymatic degradation rate and select cellooligosaccharides. This is preferable because the rate is improved.

  In the present invention, an enzyme used for hydrolysis of a cellulosic substance is referred to as cellulase, and the cellulase used in the present invention is a general term for enzymes that decompose cellulose. It is included in the cellulase referred to in the invention. Cellulase enzyme sources include, for example, cellulase-producing living cells themselves, purified enzyme secreted by cellulase-producing bacteria, and formulated purified enzyme together with excipients, stabilizers and other additives. . In the case of a cellulase preparation, the additive added thereto is not particularly limited, and the dosage form may be any of powder, granule, liquid and the like.

  The origin of cellulase is not particularly limited. For example, microorganisms that produce known cellulases include the genus Tricodederma, the genus Acremonium, the genus Aspergillus, the genus Bacillus, and the pseudomonas. (Pse-udomonas) genus, Penicillium genus, Aeromonus genus, Irpex genus, Sporotrichum genus, Humicola genus, Cellobibrio genus (Cellovibrio genus Cellobrien) Produced by Tific (1987)) and “Encyclopedia of Cellulose” (Asakura Shoten (2000)) It can be exemplified cellulase, if enzymes that degrade cellulose, not only the enzyme derived from the known bacteria, enzymes from novel microorganisms are also included in cellulase of the present invention.

The enzymatic decomposition method may be any known method, and is not particularly limited. For example, the cellulosic material is suspended in an aqueous medium, cellulase is added, and stirring or shaking is performed. And a method of performing a saccharification reaction by heating.
In the above method, the suspension method, the stirring method, the addition method / order of addition of cellulase / substrate, the concentration thereof, and other reaction conditions are appropriately adjusted so that the cellooligosaccharide can be obtained in a higher yield. In this case, the pH and temperature of the reaction solution may be within the range where the enzyme is not deactivated. Generally, when the reaction is performed at normal pressure, the temperature is 5 to 95 ° C., and the pH is 1 to 11. Range may be sufficient. Further, the pressure, temperature, and pH are appropriately adjusted so that the cellooligosaccharide can be obtained in a higher yield, as described above.

The cellooligosaccharide aqueous solution obtained by the above enzymatic decomposition can be subjected to purification treatment such as decolorization, desalting, enzyme removal, etc., if necessary. The purification method is not particularly limited as long as it is a known method. For example, activated carbon treatment, ion exchange resin treatment, chromatography treatment, microfiltration, ultrafiltration, reverse osmosis filtration and other filtration treatments, crystallization treatment, etc. are used. These may be used alone or in combination of two or more.
Among the cellooligosaccharide purification methods, the crystallization treatment is preferable because the composition of the cellooligosaccharide is easy to control.

  The present invention further relates to a ceramide composition comprising a ceramide dispersed in an aqueous medium, wherein the composition contains 0.005% by mass or more of a cellooligosaccharide relative to ceramide. The ceramide dispersant of the present invention is for uniformly dispersing ceramide. Ceramide is a component of the keratinocyte lipid of the epidermis, and the existence of 7 strains of ceramide 1 to ceramide 7 is known so far. Alternatively, natural ceramides derived from plants, active ceramides obtained by organic synthesis may be used, and those obtained by converting them to various derivatives with sugar residues or the like may be used. In the present invention, one of the above may be used alone, or two or more may be used in combination. It exists as a mixture of ceramide 2 and ceramide 5 in the hair, and as a mixture of ceramide 2 and 3 in the skin. In particular, when ceramides 1, 3, and 6 are reduced, it causes dry skin, keratosis, sensitive skin, and the like. Therefore, in the present invention, the type of ceramide can be selected according to the hair or skin condition to be improved. As an example, commercially available ceramide is shown below. For example, active ceramide 1 (chemical name N- (27-octadecanoyloxy-heptacosanoyl-)-phytosphingosine), active ceramide 2 (chemical name N-stearoyl dihydrosphingosine), active ceramide 3 (chemical name N- Stearoyl phytosphingosine, N-linoleyl phytosphingosine, N-oleoyl phytosphingosine), active ceramide 6 (chemical name N-2-hydroxystearoyl phytosphingosine) and the like.

  In the ceramide composition of the present invention, the cellooligosaccharide is blended in an amount of 0.005% by mass or more based on the ceramide. The greater the amount of dispersant added, the greater the effect, more preferably 0.05% by mass or more, and more preferably 0.1% by mass or more.

  The ceramide composition of the present invention preferably contains a fatty acid. Fatty acids have the effect of increasing the affinity between cellooligosaccharides and ceramides. Fatty acids used here include linseed fatty acid, arachidonic acid, arachidic acid, isomerized safflower fatty acid, isomerized reelic acid, isostearic acid, undecylenic acid, eicosapentaenoic acid, oleic acid, capric acid, beef tallow fatty acid, wheat germ oil fatty acid Rice bran oil fatty acid, safflower fatty acid, fatty acid (C14-28), fatty acid (C18-36), fatty acid (C20-40), dilinoleic acid, hydrogenated coconut fatty acid, stearic acid, serotic acid, soybean oil fatty acid, tetradi Sileicosanoic acid, tetradecyloctadecanoic acid, docosahexaenoic acid, palm kernel oil fatty acid, palm fatty acid, palmitic acid, sunflower fatty acid, butyloctanoic acid, partially hydrogenated beef tallow fatty acid, partially hydrogenated palm oil fatty acid, branched fatty acid (C12-31) ), Branched fatty acid (C14-28), hexadecyl ester "Cosmic acid, hexadecenoic acid, hexyl decanoic acid, behenic acid, beeswauric acid, myristic acid, coconut fatty acid, lauric acid, lanolin fatty acid, linoleic acid, linolenic acid" New Cosmetic Handbook (October 30, 2006 Nikko Chemicals Co., Ltd.) Company, Nippon Surfactant Co., Ltd., Toshi Pigment Co., Ltd., Cosmos Technical Center Co., Ltd., issued by Nikoderm Research Co., Ltd.) and those classified as fatty acids. In order to further enhance the effect of the present invention, it is preferable to use higher fatty acids among the above fatty acids. In the case of using a fatty acid, the content in the ceramide composition is not particularly limited, but is generally 0.1 to 99% by mass, preferably 0.5 to 50% by mass with respect to ceramide.

Moreover, it is preferable that the ceramide composition of this invention contains sterols. Sterols also have the effect of increasing the affinity between cellooligosaccharides and ceramides, like fatty acids. As used herein, sterols include pearl oyster sterol, oilseed rape sterol, rape asterols, avocado sterols, cholesteryl chloride, rice kasterol, cholesterol, sitosterol, dihydrocholesterol, soybean sterol, dehydrocholesterol, tall oil sterol, rapeseed sterol "New Cosmetic Handbook" such as Neorscogenin, Phytosterol, Lanosterol, and Ruscogenin (October 30, 2006 Nikko Chemicals Co., Ltd., Nippon Surfactant Co., Ltd., Toshi Pigment Co., Ltd., Cosmos Technical Center Co., Ltd., Nicoderm Co., Ltd. Research publications) can be used that include those classified as sterols . Further, cholesterol sulfate, alkenyl (C16-18) cholesteryl succinate, cholesteryl isostearate, dihydrocholesteryl isostearate, phytosteryl isostearate, cholesteryl oleate, dihydrocholesteryl oleate, fistrelyl oleate, cholesteryl succinate, fatty acid phytosteryl succinate, Cholesteryl acetate, hydroxy acid fatty acid (C10-40) (cholesteryl / lanosteryl), cholesteryl stearate, cholesteryl carbonate (cholesteryl / oleyl), cholesteryl nonanoate, dihydrocholesteryl nonanoate, hydroxy fatty acid (C14-25) cholesteryl, cholesteryl hydroxystearate , Phytosteryl hydroxystearate, branched fatty acid (C12-31) cholesteryl Branched fatty acid (C12-31) phytosteryl, macadamia nut fatty acid cholesteryl, macadamia nut fatty dihydrocholesteryl, branched fatty acid (C12-31) phytosteryl, butyric cholesteryl butyrate, dihydrocholesteryl, sterols such as lanolin acid cholesteryl or obtained by the derivatives. An example of a derivative is “New Cosmetic Handbook” (October 30, 2006, Nikko Chemicals Co., Ltd., Nippon Surfactant Co., Ltd., Toshi Pigment Co., Ltd., Cosmos Technical Center Co., Ltd., published by Nicoderm Research Co., Ltd.) Examples include those classified as sterol derivatives . When sterols are used, the content in the ceramide composition is not particularly limited, but is generally 0.1 to 99% by mass, preferably 0.5 to 90% by mass with respect to ceramide.

  The ceramide composition of the present invention can be used as a skin barrier function improving agent (for example, including a skin external preparation or a hair preparation). Hereinafter, the case where the ceramide composition of the present invention is used as a skin barrier function improving agent will be described.

  In the ceramide composition of the present invention, the cellooligosaccharide of the present invention may be used alone, as an aqueous solution or a dispersion, and in addition to the cellooligosaccharide of the present invention, a cosmetic material, a medicinal active ingredient. Or in one or more components selected from additives used in them, as granules, molded products, aqueous solutions, aqueous dispersions, pastes, gel-like cosmetics / quasi drugs / pharmaceuticals May be used. In particular, an aqueous solution, an aqueous dispersion, a paste, or a gel in the above composition may be used as a cosmetic / quasi-drug / pharmaceutical external preparation for skin.

  The ceramide composition of the present invention may contain oligosaccharides other than glucose in addition to the cellooligosaccharide of the present invention. The mixing ratio of cellooligosaccharide and oligosaccharide is not limited as long as the effect of the present invention is obtained. For example, the mass ratio of cellooligosaccharide / oligosaccharide is 0.1 / 99.9 to 99.9 / 0. .1.

  Examples of the oligosaccharide include saccharides such as galactose, fructose, mannose, arabinose, rhamnose, ribose, xylose, sorbose and their reduced products, sucrose, melibiose, trehalose, lactose, maltose, gentiobiose, laminaribiose, lactulose. Disaccharides such as xylobiose and their reduced products, lactosucrose, raffinose, maltototriose, isomaltose, palatinose, kestose, trisaccharides such as gentiosil cellobiose and their reduced products, maltotetraose, gentiosyl cellotri Tetrasaccharides such as ose and nystose and their reduced products, 5 or 6 saccharides such as maltopentaose and maltohexaose and their reduced products, β-cyclodextrin, γ-si Cyclodextrins, cyclic oligosaccharides such as dextran, indigestible dextrin, polydextrose, gum arabic, carboxymethylcellulose, guar gum, curdlan and other water-soluble polysaccharides and their reduced products, sorbitol, xylitol, multirole, mannitol, lactitol Sugar alcohols such as Even if these oligosaccharides are used as they are, the hydroxyl groups in the chemical structure are subjected to chemical treatments such as carboxylation, ethylation, methylation, and sulfate esterification for the purpose of improving solubility. It is also possible to use a derivative.

  Constituents in the present invention are oligosaccharides other than cellooligosaccharides, cosmetic materials, pharmaceutical medicinal ingredients, pigments, fragrances, metals, ceramics or excipients, disintegrants, binders, fluidizers, lubricants, taste masking. It is an additive such as an agent, a colorant, a sweetener, a solvent, an oil, a surfactant, a thickener, a gelling agent, etc., in any form such as powder, crystal, oil, liquid, semi-solid However, for example, according to “Japan Pharmacopoeia” (published by Yodogawa Shoten), “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo), “Cosmetic Raw Material Standards”, and “Composition Standards by Cosmetic Variety” (all published by Yakuji Nippo) Those described can be used.

Further, they may be subjected to processing such as coating and liposome formation for various purposes. These constituent components may be used alone or in combination. The amount of the constituent component added is 0.01% to 99%.
The ceramide composition of the present invention can be processed by known methods such as dissolution, mixing, dispersion, granulation, melting / solidification, compression, and drying.

The cosmetic / pharmaceutical product comprising the ceramide composition mainly comprising the cellooligosaccharide of the present invention and one or more components selected from cosmetic materials, medicinal medicinal ingredients, or additives used in them. Although a quasi-drug / pharmaceutical production method will be described, the effect of the present invention is not limited to the following method.
The method for adding each component is not particularly limited as long as it is a commonly used method, but 1) Cellooligosaccharide and components are added simultaneously and mixed / dispersed. 2) Cellooligosaccharide and specific components Even if another component is added and mixed / dispersed after mixing / dispersing in advance, 3) After mixing / dispersing two or more components in advance, cellooligosaccharide is added and mixed / dispersed. Or a combination of these addition methods.

  The devices used here are small suction transport devices, pneumatic transport devices, bucket conveyors, pressure-feed transport devices, vacuum conveyors, vibratory quantitative feeders, sprays, funnels, etc. May be. The mixing method of each component is not particularly limited as long as it is a normal method, but a container rotary mixer such as a V type, W type, double cone type, container tack type mixer, or high-speed stirring is used. A stirring mixer such as a mold, a universal stirring type, a ribbon type, a pug type, and a Nauta type mixer, a high-speed fluid mixer, a drum mixer, and a fluidized bed mixer may be used. A shaker mixer such as a shaker can also be used.

  The dispersion method is not particularly limited as long as it is a commonly performed dispersion method, but it is a one-way rotation type such as a portable mixer, a three-dimensional mixer, a side mixer, a multi-axis rotation type, a reciprocating reversal type, a vertical movement type, a rotation + up and down Mixing method using stirring blades such as mobile type, pipe type, jet type stirring and mixing method such as line mixer, gas blowing type stirring and mixing method, high shear homogenizer, high pressure homogenizer, ultrasonic homogenizer, etc. The method may also be a container-shaking mixing method using a shaker, or a combination of these methods.

  Further, in the above mixing and dispersion, there is no particular limitation on the order of adding an aqueous medium to which a surfactant, a thickener, and a gelling agent are added to water or a water / organic solvent as necessary. After adding aqueous medium to cellooligosaccharide and dissolving / dispersing it, add other components 2) Add aqueous medium to component and dissolving / dispersing it before adding cellooligosaccharide Alternatively, 3) after mixing / dispersing the cellooligosaccharide and the constituent components in advance, an aqueous medium may be added, or a method of combining these may be used. Each liquid such as aqueous solution, dispersion, emulsion, etc. obtained here, each semi-solid cosmetic / quasi-drug / pharmaceutical such as paste, gel, etc. are dried as necessary, granulated, coated, molded, etc. May be processed.

  The granulation / coating method is not particularly limited as long as it is a known method, but either a stirring method or a fluidized bed method may be used, or a method combining them may be used. Examples of the agitation granulator include a one-way rotary type such as a portable mixer, a three-dimensional mixer, and a side mixer, a multi-axis rotary type, a reciprocating reversal type, a vertical movement type, a rotation + vertical movement type agitator, and a fluidized bed type. An upper spray type, a central spray type, a lower spray type, a combined stirring type, a central can jet type, a Wurster type and the like can be mentioned. Moreover, you may give the dry granulation which uses a roller compactor.

  Regarding the coating, a granulated product may be obtained in advance, and a known coating may be applied thereto, or after coating, another coating may be applied to form a multilayer. As a spraying method of the coating agent, a method of spraying an active ingredient solution / dispersion using a pressure nozzle, a two-fluid nozzle, a four-fluid nozzle, a rotating disk, an ultrasonic nozzle, etc., and an active ingredient solution / dispersion from a tubular nozzle are used. Any method of dropping may be used. When the active ingredient solution / dispersion is added, the active ingredient solution / dispersion may be layered or coated such that the active ingredient is laminated on the surface of the cellooligosaccharide particles, or may be supported on the cellooligosaccharide. As a binding solution, a mixture of cellooligosaccharide and other components may be granulated in a matrix. The effect is the same whether the layering or coating is wet or dry.

  The molding method is not particularly limited as long as it is a commonly performed method, but a mold may be used, and a known molding method such as compression, melting, injection, rolling, etc. can be applied, and a method combining these But you can. Examples of molding machines used here include compression molding machines, melt molding machines, injection molding machines, and rolling molding machines. Confectionery / cosmetics / pharmaceutical molding machines, cooked rice molding machines, compressed molding machines, packaging machines Well-known molding machines, such as a rice cake manufacturing apparatus, a dumpling / wrapping molding machine, and a foundation substrate compression molding machine, can be used. In particular, regarding compression molding, a method of compression molding into a desired shape using a mold, or a method of pre-compressing into a sheet shape and then cleaving into a desired shape may be used. As the compression molding machine, for example, a roller press such as a hydrostatic press, a briquetting roller press, a smooth roller press, a compressor such as a single punch tablet press, or a rotary tablet press can be used. .

Next, an example of the components used in the production of the ceramide composition described above will be described.
For example, as a cosmetic material or additive used therein, in addition to the cellooligosaccharide of the present invention, a moisturizer, amino acid, vitamins, hydrocarbon, higher fatty acid, ester, silicon, surfactant, A pH adjuster and water may be added. These cosmetic materials or additives can be used alone or in combination of two or more.

  For example, as a moisturizing agent, polyethylene glycol, propylene glycol, glycerin, 1,3-butylene glycol, sorbitol, maltitol, chondroitin sulfate, collagen, sodium lactate, dl-pyrrolidone carboxylic acid, yocuinine extract, soybean lecithin, etc. Examples include those classified as moisturizers in “Cosmetic Raw Material Standards” and “Composition Standards by Cosmetic Variety” (both published by Yakuji Nippo).

  Examples of amino acids include neutral amino acids such as glycine, alanine, valine, leucine, isoleucine, serine, threonine, tryptophan, cystine, methionine, proline, hydroxyproline, glutamine, asparagine, acidic amino acids such as aspartic acid and glutamic acid, arginine And basic amino acids such as histidine, lysine and hydroxylysine, etc., which are classified as amino acids in “Cosmetic Raw Material Standards” and “Composition Component Standards by Cosmetic Variety” (all published by Yakuji Nippo).

Examples of hydrocarbons include those classified as hydrocarbons in “Cosmetics raw material standards” such as liquid paraffin, paraffin, suclan, petrolatum, etc., and “Mixed ingredient specifications by cosmetic variety” (all published by Yakuji Nippo).
Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, beheric acid, oleic acid, hydroxystearic acid, undecylenic acid, isostearic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, etc. Are classified as higher fatty acids in “Cosmetic Raw Material Standards” (published by Yakuji Nippo).

  Esters include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyl decyl dimethyloctanoate, cetyl lactate, myristyl lactate, Lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl hydroxystearate, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate Glycerin, di-2-heptylundecanoic acid, glycerin tri-2-ethylhexylate, trimethylol stearate torii Bread, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimyristate, tri-2-heptylundecanoic acid glyceride, castor oil Shikoku methyl ester, 2-hexyldecyl myristate, 2-hexyldecyl palmitate Categorized as esters in "Cosmetics raw material standards" such as 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, triethyl citrate, etc. Things.

  Examples of silicon include “coating raw materials such as chain polysiloxanes such as dimethylpolysiloxane and methylphenylpolysiloxane, cyclic siloxanes such as decamethylcyclopentasiloxane and decamethylcyclohexasiloxane, and cross-linked stitched silicone resins. Examples include silicon described in “Standard” and “Composition Component Standards by Cosmetic Variety” (both published by Yakuji Nippo).

  Examples of the surfactant include acyl amino acid salts such as acyl glutamate, higher alkyl sulfate salts such as sodium laurate, sodium palmitate, sodium lauryl sulfate, potassium lauryl sulfate, polyoxyethylene lauryl sulfate triethanolamine, In addition to anionic surfactants such as alkyl ether sulfates such as sodium oxyethylene lauryl sulfate and N-acyl sarcosine salts such as sodium lauroyl sarcosine, alkyltrimethylammonium salts such as stearyltrimethylammonium chloride and lauryltrimethylammonium chloride, Distearyldimethylammonium dialkyldimethylammonium chloride, chloride (N, N′-dimethyl-3,5-methylenepiperidinium), cetyl pitidichloride Alkylpyridinium salts such as um, alkyl quaternary ammonium salts, alkylamine salts such as polyoxyethylene alkylamine, cationic surfactants such as polyamine fatty acid derivatives, amyl alcohol fatty acid derivatives, 2-undecyl-N, N, N- (Hydroxyethyl carboxymethyl) 2-imidazoline sodium, 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt and the like imidazoline-based amphoteric surfactants, 2-heptadecyl-N-carboxymethyl- Amphoteric surfactants such as betaine amphoteric surfactants such as N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, alkylbetaine, amide betaine, sulfobataine, sorbitan nomooleate, sorbitan mono Sorbitan such as isostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan sesquioleate, sorbitan trioleate, glycerol sorbitan with panta-2-ethylhexyl acid, diglycerol sorbitan tetra-2-ethylhexylate Fatty acid esters, glyceryl monostearate, α, α'-oleic acid pyroglutamate glycerin, glycerin polyglycerin fatty acids such as monostearic acid glycerin malic acid, propylene glycol fatty acid esters such as propylene glycol monostearate, hydrogenated castor oil Derivatives, glycerin alkyl ethers, polyoxyethylene-sorbitan monostearate, polyoxyethylene-sorbitan monooleate, polio Polyoxyethylene-sorbitan fatty acid esters such as siethylene-sorbitan tetraoleate, polyoxyethylene-sorbitol monolaurate, polyoxyethylene-sorbitol monooleate, polyoxyethylene-sorbitol pentaoleate, polyoxyethylene-sorbitol mono Stearate, polyoxyethylene-glycerin monoisostearate, polyoxyethylene-glycerin fatty acid esters such as polyoxyethylene-glycerin triisostearate, polyoxyethylene monooleate, polyoxyethylene distearate, polyoxyethylene Monodiolates, polyoxyethylene fatty acid esters such as ethylene glycol stearate, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil Polyoxyethylene such as polyoxyethylene hydrogenated castor oil monoisostearate, polyoxyethylene hydrogenated castor oil triisostearate, polyoxyethylene hydrogenated castor oil monopyroglutamic acid monoisostearic acid diester, polyoxyethylene hydrogenated castor oil maleic acid, etc. Nonionic surfactants such as castor oil hardened castor oil derivatives and the like are classified as surfactants in “Cosmetic Raw Material Standards” and “Composition Component Standards by Cosmetic Variety” (all published by Yakuji Nippo).

  Examples of pH adjusters include “cosmetic raw material standards” such as lactic acid-sodium lactate, citric acid-sodium citrate, phosphoric acid-sodium phosphate, acetic acid-sodium acetate, Mcvine reagent, etc. And buffering agents described in Pharmaceutical Affairs Daily).

Examples of medicinal medicinal ingredients include antipyretic analgesic / anti-inflammatory drugs, hypnotic sedatives, drowsiness preventives, antipruritics, pediatric analgesics, stomachic drugs, antacids, digestives, cardiotonic drugs, arrhythmic drugs, antihypertensive drugs, vasodilators Drugs, diuretics, anti-ulcer drugs, intestinal adjusters, osteoporosis drugs, antitussive expectorants, anti-asthma drugs, antibacterial agents, frequent urination improvers, nourishing tonics, vitamins, etc. Is the target. The medicinal component can be used alone or in combination of two or more.
Next, additives used in pharmaceuticals / quasi drugs are described.

  Excipients include starch acrylate, L-aspartic acid, aminoethylsulfonic acid, aminoacetic acid, candy (powder), gum arabic, gum arabic powder, alginic acid, sodium alginate, pregelatinized starch, inositol, ethylcellulose, ethylene Vinyl acetate copolymer, sodium chloride, olive oil, kaolin, cacao butter, casein, fructose, pumice grains, carmellose, carmellose sodium, hydrous silicon dioxide, dry yeast, dry aluminum hydroxide gel, dry sodium sulfate, dry magnesium sulfate, agar, Agar powder, xylitol, citric acid, sodium citrate, disodium citrate, glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay granules, croscarmellose nato Um, cross polyvinylpyrrolidone, magnesium aluminate silicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, cinnamon powder, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (grain) , Synthetic aluminum silicate, synthetic hydrotalcite, sesame oil, wheat flour, wheat starch, wheat germ powder, rice, rice starch, potassium acetate, calcium acetate, cellulose acetate phthalate, safflower oil, white beeswax, zinc oxide, titanium oxide , Magnesium oxide, β-cyclodextrin, dihydroxyaluminum aminoacetate, 2,6-di-butyl-4-methylphenol, dimethylpolysiloxane, tartaric acid, potassium hydrogen tartrate, baked gypsum, sucrose fatty acid ester Tellurium Magnesium Hydroxide, Aluminum Hydroxide / Gel, Aluminum Hydroxide / Sodium Bicarbonate Coprecipitate, Magnesium Hydroxide, Suclan, Stearyl Alcohol, Stearic Acid, Calcium Stearate, Polyoxyl Stearate, Magnesium Stearate, Sterotex HM , Purified gelatin, purified shellac, purified sucrose, purified sucrose spherical granules, cetostearyl alcohol, cetopolyethylene glycol, gelatin, sorbitan fatty acid ester, D-sorbitol, tricalcium phosphate, soybean oil, soybean unsaponifiable matter, soybean lecithin, skim milk powder , Talc, ammonium carbonate, calcium carbonate, magnesium carbonate, neutral anhydrous sodium sulfate, low-substituted hydroxypropyl cellulose, dextran, dextrin, natural silicic acid Luminium, corn starch, tragacanth powder, silicon dioxide, calcium lactate, lactose, white petrolatum, sucrose, sucrose / starch spherical granules, green leaf extract powder, naked malt green juice dry powder, honey, paraffin, potato starch, semi-digested body Starch, human serum albumin, hydroxypropyl starch, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, phytic acid, glucose, glucose hydrate, partially pregelatinized starch, pullulan, propylene glycol, powdered reduced maltose starch syrup, powdered cellulose, pectin, bentonite , Sodium polyacrylate, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polystyrene Sodium sulfonate, polyvinyl acetal diethylaminoacetate, polyethylene glycol, maltitol, maltose, D-mannitol, water candy, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granule, magnesium aluminate metasilicate, methylcellulose , Cottonseed powder, cottonseed oil, mole, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, medicinal charcoal, peanut oil, aluminum sulfate, calcium sulfate, granular corn starch, liquid paraffin, dl-malic acid, phosphorus Acid-hydrogen calcium, calcium hydrogen phosphate, calcium hydrogen phosphate granulated product, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, phosphoric acid diwater These include those classified as excipients in “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) and “Japan Pharmacopoeia” (published by Yodogawa Shoten), such as sodium. In addition, two or more kinds can be used in combination.

  Disintegrants include croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, celluloses such as low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch, rice starch, wheat starch, corn starch, potato “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) such as starches, starches such as partially pregelatinized starch, synthetic polymers such as cross polyvinyl pyrrolidone and cross polyvinyl pyrrolidone copolymer, “Japan Pharmacopoeia” (Yodogawa Shoten) Issued) is classified as a disintegrant. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.

  As binders, sugars such as sucrose, glucose, lactose, fructose, sugar alcohols such as mannitol, xylitol, maltitol, erythritol, sorbitol, gelatin, pullulan, carrageenan, locust bean gum, agar, gluconannan, xanthan gum, tamarind Water-soluble polysaccharides such as gum, pectin, sodium alginate, gum arabic, etc., celluloses such as crystalline cellulose, powdered cellulose, hydroxypropylcellulose, methylcellulose, starches such as pregelatinized starch, starch paste, polyvinylpyrrolidone, carboxyvinyl polymer, Synthetic polymers such as polyvinyl alcohol, inorganic compounds such as calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, magnesium aluminate silicate etc. "(Yakujinipposha Co., Ltd. issued), mention may be made of those which are classified" as a binding agent in the Japanese Pharmacopoeia "(Hirokawa Shoten). Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.

  As fluidizers, fluidized into “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) and “Nippon Pharmacopoeia” (published by Yodogawa Shoten) such as silicon compounds such as hydrous silicon dioxide and light anhydrous silicic acid. The thing classified as an agent can be mentioned. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.

  Lubricants include: “Pharmaceutical Additives Encyclopedia” such as magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid ester and talc (published by Yakuji Nippo Co., Ltd.), “Japan Pharmacopoeia” (published by Yodogawa Shoten) And those classified as lubricants. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.

As a corrigent, "Pharmaceutical Additives Encyclopedia" such as glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, 1-menthol, etc. (published by Yakuji Nippo Co., Ltd.) ), "Japanese Pharmacopoeia" (published by Yodogawa Shoten), those classified as flavoring agents. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
As perfumes, oils such as orange, vanilla, strawberry, yogurt, menthol, fennel oil, cinnamon oil, spruce oil, mint oil, etc., “Pharmaceutical Additives Encyclopedia” such as green tea powder (published by Yakuji Nippo Co., Ltd.), Mentioned as “fragrances and fragrances” by “Japanese Pharmacopoeia” (published by Yodogawa Shoten). Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.

As coloring agents, “Drugs for Food Additives” such as Food Red No. 3, Food Yellow No. 5, Food Blue No. 1, etc., copper chlorofin sodium, titanium oxide, riboflavin, etc. (published by Yakuji Nippo Co., Ltd.) And those classified as colorants by “Japanese Pharmacopoeia” (published by Yodogawa Shoten). Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
Sweeteners include aspartame, saccharin, dipotassium glycyrrhizinate, stevia, maltose, maltitol, starch syrup, and amacha powder, etc. (published by Yakuji Nippo Co., Ltd.), “Japanese Pharmacopoeia” (Yodogawa) (Published by a bookstore) can be listed as sweeteners. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.

Solvents are not particularly limited as long as they are used in pharmaceuticals / quasi drugs, and include, for example, “pharmaceutical additives encyclopedia” (alcohols such as methanol and ethanol, ketones such as acetone, etc.) Nikkansha Co., Ltd.) and “Nippon Pharmacopoeia” (published by Yodogawa Shoten) include those classified as solvents. They can be used alone or in combination of two or more.
Examples of fats and oils include stearic acid monoglyceride, stearic acid triglyceride, stearic acid sucrose ester, paraffins such as liquid paraffin, hard oils such as carnauba wax and hardened castor oil, castor oil, stearic acid, stearyl alcohol, polyethylene The oils and fats listed in “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) and “Nippon Pharmacopoeia” (published by Yodogawa Shoten) such as glycol are listed. Can also be used together.

As a thickener, for example, “pharmaceutical additive encyclopedia” such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, ethylcellulose, gum arabic, starch paste, etc. (Published by Yakuji Nippo Co., Ltd.), “Japanese Pharmacopoeia” (published by Yodogawa Shoten), and thickeners can be used. They can be used alone or in combination of two or more. is there.
Examples of the surfactant include phospholipid, glycerin fatty acid ester, polyethylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene nonylphenyl ether, Polyoxyethylene polyoxypropylene glycol, polyoxyethylene sorbitan sun monolaurate, polysorbate, sorbitan monooleate, glyceride monostearate, monooxyethylene sorbitan monopalmitate, monooxyethylene sorbitan monostearate, polyoxymonooleate "Pharmaceutical Additives Encyclopedia" such as ethylene sorbitan, sorbitan monopalmitate, sodium lauryl sulfate ) Issued), "Japanese Pharmacopoeia" (published by Hirokawa Shoten) those classified as a surfactant can be mentioned, even using it alone, it is free to combination of two or more.

  Examples of the gelling agent include animal gelling agents such as gelatin, agar, xanthan gum, guar gum, gum arabic, curdlan, locust bean gum, carboxymethyl cellulose, hydroxyethyl cellulose, cellulose, microcrystalline cellulose, microcrystalline cellulose and the like. That are classified as gelling agents in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) and “Nippon Pharmacopoeia” (published by Yodogawa Shoten), such as chemically synthesized polymers such as functional polysaccharides and polyvinylpyrrolidone Even if it is used alone, two or more kinds can be used in combination.

Examples of cosmetics / quasi drugs / pharmaceuticals using the ceramide composition of the present invention will be given below.
As cosmetics, for example, perfume oil, hair oil, polish oil, ski oil, bottle oil, set lotion, hair stick, hair cream, pomade, hair spray, hair liquid etc., hair tonic, hair treatment, hair lotion etc. Hair coloring, hair spray such as color spray, color rinse, scalp, hair wash, shampoo, etc., hair rinse, oil rinse, cream rinse, body rinse, facial rinse, cleansing cream, face wash, cleansing Facial cleansers such as milk, cleansing lotions and powders, packs, creams such as oily creams, neutral creams and weakly acidic creams, milk lotions and skin milks, skin lotions for dry skin, skin lotions for normal skin, oily skin Lotion for men, lotion for men, men lotion , Lipsticks such as after-shave lotion, makeup base, foundation, funny, lipstick, lipstick, ripple rouge, lip gloss, lip balm, eye shadow, eyeliner, eye cream, eyebrow, eyelash cosmetic, eye Makeup remover, eye makeup, blusher, eyebrow pencil, eyebrow blush, mascara and other eyebrows cheek cosmetics, nail enamel, nail cream, nail polish, pedicure, enamel remover, beauty remover, nail polish, perfume, eau de cologne, Cologne, Eau de Cologne, Cologne, Bath salt, Bath oils such as bath oil, Oils containing olive oil, cocoon oil, Baby oil etc., Tanning cosmetics, Cold cream, Tanning cosmetics, Shaving products Described in “Cosmetic Science Guidebook” (published by Japan Cosmetic Engineers Association, published by Yakuji Nippo), such as shaving creams such as creams, shaving foams, pre-shave cosmetics, talcum powder, body powders, bath powders, perfume powders, etc. May be used for those classified into these.

  Examples of quasi-drugs / pharmaceuticals include extracts, suspensions, emulsions, spirits, soaking agents, decoctions, tinctures, fragrances, fluid extracts, liquids, aerosols, etc. Agent, mouthwash, inhalant, poultice, disinfectant, ear and nose solution, wiping agent, injection agent, coating agent, spray agent, bath agent, oily, emulsion, suspension, water-soluble, hydrogel, Liquid preparations, external preparations and eye drops described in the “Pharmacology Manual Second Edition” (published by Nanzan Hall) such as ointments, plasters, poultices, lotions, liniments, eye drops, etc. A dosage form such as an agent may be mentioned, and it may be used for those classified into these.

The present invention will be described based on examples, but the present invention is not limited thereto.
<Method for producing cellooligosaccharide>
[Production Example 1]
Trichoderma reesei GL-1 strain (Incorporated Administrative Agency, National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center, receipt number FERM BP-10323) was inoculated on a normal agar medium and cultured at 28 ° C. for 7 days. 1 spore ears, 1 g polypeptone, 0.5 g yeast extract, 2 g potassium phosphate, 1.5 g ammonium sulfate, 0.3 g magnesium sulfate, 0.3 g calcium chloride, 1 mL trace element (6 mg boric acid, ammonium molybdate) 26 mg of tetrahydrate, 100 mg of iron chloride (3) hexahydrate, 40 mg of copper sulfate pentahydrate, 8 mg of manganese sulfate tetrahydrate, and 200 mg of zinc sulfate heptahydrate were dissolved in 100 mL of purified water in total. ), Adecanol 1 mL, crystalline cellulose (product name, manufactured by Asahi Kasei Chemicals) 10 g of PH-101) was inoculated into a medium suspended and dissolved in 1 L of purified water in total, and cultured with aeration at 28 ° C. for 5 days. During the culture, the pH of the medium was adjusted to 2.8 to 4.7 using an aqueous phosphoric acid solution and an aqueous sodium hydroxide solution. The cultured liquid is centrifuged, the supernatant is sterilized with a microfiltration membrane having an opening of 0.46 μm, and the filtrate is ultrafiltered with a molecular weight cut off of 13,000 (trade name: Microza Pencil type module ACP manufactured by Asahi Kasei Chemicals). -0013) was concentrated 10 times by volume to obtain a crude enzyme.

  Next, use a commercially available softwood-derived dissolving pulp, and hydrolyze it with a hydrochloric acid concentration of 0.4% aqueous hydrochloric acid at 120 ° C. for 1 hour to wash the acid-insoluble residue and filter to obtain a wet cake. It was. Using this wet cake as an aqueous dispersion with a concentration of 10% cellulose, an ultra-high performance disperser / wet pulverizer (manufactured by Ashizawa Co., Ltd., trade name: Pearl Mill RL φ1mm zirconia bead filling rate 80%) A grinding treatment was performed to obtain a cellulose fine particle dispersion (average polymerization degree 220, diethyl ether soluble matter content 0.7%, average particle diameter 0.7 μm, colloidal component content 51.5%).

The ground cellulose was suspended and dissolved in a 50 mM acetic acid-sodium acetate buffer (pH 4.5) so that the crude cellulose was 2% by mass and the protein concentration was 0.25%, and the total volume was 1000 mL. . The glass flask was placed in a 55 ° C. water bath and reacted for 4 hours while stirring the interior. After completion of the reaction, 300 μL of the reaction solution was dispensed in a suspended state, the enzyme and undegraded cellulose were removed using an ultrafiltration module (fractional molecular weight 10,000), and then the sugar concentration was analyzed by high performance liquid chromatography. . The sugar concentration of the reaction solution was cellotriose to cellohexaose 0.2% by mass, cellobiose 1.5% by mass, and glucose 0.3% by mass.
The reaction solution was filtered through an ultrafiltration membrane having a molecular weight cut off of 13000 (trade name Micro-The Pencil type module ACP-0013 manufactured by Asahi Kasei Chemicals), and the resulting filtrate was deionized with a cation / anion exchange resin. Distillation was performed at 70 ° C. under reduced pressure to obtain an aqueous solution having a sugar concentration of 20 times.

  100 mL of the cellooligosaccharide aqueous solution obtained above was introduced into a 200 mL glass flask, cooled to 70 ° C. to 5 ° C. at a rate of 10 ° C. per hour while stirring, and then ethanol was added to water for crystallization. The cellooligosaccharide crystallized in the aqueous solution was filtered under reduced pressure, dried, pulverized and sieved to obtain the cellooligosaccharide powder of Production Example 1. The sugar composition of the obtained cellooligosaccharide powder is shown in Table 1.

[Production Example 2]
Commercial cellobiose, cellotriose, cellohexaose (manufactured by Sigma Aldrich) and glucose (manufactured by Wako Pure Chemical Industries, Ltd.) and glucose were mixed to obtain the cellooligosaccharide powder of Production Example 2. The sugar composition of the obtained cellooligosaccharide powder is shown in Table 1.

<Method for producing aqueous dispersion of ceramide>
1) Composition of aqueous dispersion Table 2 shows an example of a composition for producing an aqueous dispersion of ceramide.

2) Method for producing aqueous dispersion First, ceramide and a lipid component were mixed in the composition shown in Table 2, 70 mass% of a cellooligosaccharide aqueous solution having a predetermined concentration was added to 30 mass% of the lipid, and this mixture was added at 80 ° C. Heated, then sonicated for 10 minutes and cooled at 10 ° C. This operation was repeated 4 times.
In Comparative Example 1, only purified water obtained by removing cellooligosaccharide was added from the above-mentioned cellooligosaccharide aqueous solution, and a ceramide aqueous dispersion was similarly prepared. In addition, Comparative Example 2 uses raffinose (trade name Oligo GGF, manufactured by Asahi Kasei Chemicals) instead of the above-mentioned cellooligosaccharide, Comparative Example 3 uses trehalose (Tradehalose manufactured by Hayashibara Corporation), and Comparative Example 4 uses maltitol (Hayashibara). A ceramide aqueous dispersion was prepared in the same manner using a powdered mabit (trade name).
3) Observation of formation state of lamellar liquid crystal The lamellar liquid crystal formation was visually evaluated with a polarizing microscope for the number and size of the Maltese cross images. In each Example in which the cellooligosaccharide was blended, ceramide maltese cloth was confirmed by microscopic observation. On the other hand, no Maltese cross was confirmed in the comparative example in which the cellooligosaccharide was not blended. FIG. 1 shows a microscope observation image of the dispersion obtained in Example 1, and FIG. 2 shows a microscope observation image obtained in the comparative example. As can be seen from the above results, it was shown that ceramide can be uniformly dispersed in an aqueous medium by blending cellooligosaccharide. Moreover, as a result of visually observing the composition of each Example in which the Maltese cloth was confirmed as described above, the ceramide was not dispersed or separated, and was uniformly dispersed. In contrast, in Comparative Example 1, ceramide separation and water separation were easily confirmed.
In Examples 1 and 2, cello-oligosaccharides having different production methods were used, but the formation of lamellar liquid crystals was equivalent. The obtained ceramide composition was sealed and stored at 80 ° C. for 12 hours. As a result, Example 2 was less colored than Example 1.

4) Storage stability test The ceramide aqueous dispersions obtained in Example 4 and Comparative Examples 1 to 4 were treated at 40 ° C. with a relative humidity of 15% (low humidity), 35% (normal humidity), and 75% (high humidity). ), And stored for 4 hours under open conditions. Before and after storage, the weight was measured and the residual moisture content was quantified. The higher the residual moisture content (there is 20% or more), the better the storage stability. In addition, comparing the results of each storage condition, the smaller the variation in the residual moisture content, the better the storage stability.
The moisture residual ratio of Example 4 was 24.5% (relative humidity 15%), 25.1% (relative humidity 35%), and 24.6 (relative humidity 75%). Further, in Example 4, as a result of microscopic observation before and after the storage, the Example maintained the lamellar liquid crystal state even after the storage.
On the other hand, the moisture residual ratio of Comparative Example 1 is 11.5% (relative humidity 15%), 12.1% (relative humidity 35%), 13.8 (relative humidity 75%). In all of the low humidity, normal humidity, and high humidity, the examples clearly had better storage stability.
Moreover, the moisture residual rate of the comparative example 2 is 22.0% (relative humidity 15%), 24.2% (relative humidity 35%), 27.9% (relative humidity 75%). The water residual ratio was 18.5% (relative humidity 15%), 24.6% (relative humidity 35%), and 27.3% (relative humidity 75%). In Comparative Examples 2 and 4, although the moisture residual rate was high under high humidity, the examples had excellent moisture residual rates at low humidity and normal humidity. In Example 4, the variation in the residual moisture content was small compared to Comparative Examples 2 and 4, and the storage stability was excellent.
The residual moisture rate of Comparative Example 3 was 18.2% (relative humidity 15%), 16.5% (relative humidity 35%), 22.1% (relative humidity 75%), and Example 4 was low. In all of humidity, normal humidity, and high humidity, the examples clearly had better storage stability.

  The ceramide dispersant containing the cellooligosaccharide of the present invention can disperse the hardly soluble / hardly dispersible ceramide uniformly in an aqueous medium and can be stably stored. It can be suitably used for hair preparations.

FIG. 1 shows a microscopic image of the dispersion obtained in Example 1. FIG. 2 shows a microscope observation image obtained in Comparative Example 1.

Claims (3)

A ceramide composition comprising ceramide dispersed in an aqueous medium using a ceramide dispersant containing cellooligosaccharide, comprising 0.005% by mass or more of cellooligosaccharide relative to ceramide, and further 0.5 to A ceramide composition comprising 50% by mass of a fatty acid and 0.5 to 90% by mass of a sterol and / or a sterol derivative with respect to ceramide. The cellobiose content in the cellooligosaccharide is 70% by mass or more, and the content of one or more sugars selected from cellotriose, cellotetraose, cellopentaose and cellohexaose is 30% by mass or less. Ceramide composition. The ceramide composition according to claim 1 or 2, which is used as a skin barrier function improving agent.